[Mitochondrial diseases. Diagnostic light and electron microscopic changes in muscle biopsies from patients with...

Mitochondrial myopathy can be caused by several metabolic defects in the mitochondria. Cells with high levels of oxidative metabolism, such as skeletal muscle, myocardium and brain cells, are particularly vulnerable to these defects. We describe the structural changes in muscle biopsies from 49 patients with mitochondrial myopathy. The younger patients were often symptom-free, but the possibility of a genetic defect was suggested by the family history. "Ragged-red fibres" were found in 10% of the biopsies. Typical paracrystalline inclusions were seen in the mitochondria of the oldest patients. Electron-lucent matrix and increased thickness of the inner membranes of the mitochondria in particular were found in the younger patients. Disorganization of cristae, with cristolysis and unfolding of the cristae was also found. We suggest that structural mitochondrial changes in mitochondrial myopathy constitute a stepwise process and that the mitochondrial alterations of the cristae may represent an early stage in the morphogenesis of mitochondrial disease.